title: Discontinuation of antiplatelet study medication and risk of recurrent stroke and cardiovascular events: results from the PRoFESS study.
abstract: BACKGROUND
  Several case control studies have reported an increased risk of cardiovascular events following discontinuation of antiplatelet agents in high-risk patients. We therefore sought to investigate the risk of recurrent stroke and cardiovascular events following discontinuation of antiplatelet study medication in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial, a large randomized secondary stroke prevention study.
  
  
  METHODS
  The recurrent stroke and cardiovascular event rates following discontinuation of aspirin plus extended-release dipyridamole (ASA + ERDP) or clopidogrel were compared to the event rates in the on-treatment populations (patients who had discontinued their antiplatelet medication due to an outcome event were kept in the on-treatment population in order not to underestimate the on-treatment stroke rate).
  
  
  RESULTS
  In 7,212 treated ASA + ERDP patients, the stroke incidence rate for the on-treatment group was 729 strokes with an average exposure of 17,048 person-years (0.12 per 1,000 person-days). For 7,864 treated clopidogrel patients, the stroke incidence rate for the on-treatment group was 737 strokes with an average exposure of 18,715 person-years (0.11 per 1,000 person-days). ASA + ERDP was discontinued in 2,843 patients (in 57.7% due to an adverse event, 28.2% noncompliance, 1.4% loss to follow-up, 4.5% withdrawal of consent and 8.1% other/nonspecified reasons) and clopidogrel was permanently discontinued in 2,176 patients (49.0% due to an adverse event, 34.2% noncompliance, 1.8% loss to follow-up, 5.3% withdrawal of consent and 9.7% other/nonspecified reasons). Within 30 days, a recurrent stroke occurred in 31 patients (0.37 per 1,000 person-days) after discontinuation of ASA + ERDP and in 15 patients (0.24 per 1,000 person-days) after discontinuation of clopidogrel. This corresponds to an absolute excess risk of 0.77% within 30 days after discontinuation of ASA + ERDP and 0.40% within 30 days after discontinuation of clopidogrel compared with the on-treatment study populations. A combined vascular endpoint (stroke, myocardial infarction, vascular death) occurred in 68 patients (0.82 per 1,000 person-days) within 30 days after discontinuation of ASA + ERDP and in 47 patients (0.75 per 1,000 person-days) within 30 days after discontinuation of clopidogrel. This corresponds to an absolute excess risk of 2.02% within 30 days after discontinuation of ASA + ERDP and 1.83% within 30 days after discontinuation of clopidogrel compared with the on-treatment study populations.
  
  
  CONCLUSIONS
  Discontinuation of antiplatelet medication after ischemic stroke should be advocated only when the risk and severity of bleeding clearly outweigh the risk of cardiovascular events.
authors.affiliation: Department of Neurology, University of Duisburg-Essen, Essen, Germany. christian.weimar@uk-essen.de
authors.forename: Christian
authors.initials: C
authors.lastname: Weimar
authors.forename: Dan
authors.initials: D
authors.lastname: Cotton
authors.forename: Nanshi
authors.initials: N
authors.lastname: Sha
authors.forename: Ralph L
authors.initials: RL
authors.lastname: Sacco
authors.forename: Philip M W
authors.initials: PM
authors.lastname: Bath
authors.forename: Ralph
authors.initials: R
authors.lastname: Weber
authors.forename: Hans Christoph
authors.initials: HC
authors.lastname: Diener
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use*; D000068342:Aspirin, Dipyridamole Drug Combination; D000077144:Clopidogrel; D004176:Dipyridamole / Q000008:administration & dosage / Q000627:therapeutic use*; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D012306:Risk; D055502:Secondary Prevention; D020521:Stroke / Q000188:drug therapy* / Q000517:prevention & control; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000068342:Aspirin, Dipyridamole Drug Combination; D004338:Drug Combinations; D010975:Platelet Aggregation Inhibitors; D004176:Dipyridamole; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin